Apparatus and method for tandem ICP/FAIMS/MS

ABSTRACT

A method and an apparatus for selectively transmitting ions produced by an inductively coupled plasma ionization technique is disclosed. Ions produced within the plasma source are provided to a FAIMS analyzer within a low pressure chamber of a mass spectrometer and in fluid communication with the plasma source for receiving ions therefrom. The ions are separated in FAIMS and at least some of the ions are provided to the mass spectrometer after separation.

This application claims the benefit of provisional application60/189,085 filed on Mar. 14, 2000.

FIELD OF THE INVENTION

The present invention relates to an apparatus and method for separatingions, more particularly the present invention relates to an apparatusand method for separating ions based on the ion focusing principles ofhigh field asymmetric waveform ion mobility spectrometry (FAIMS).

BACKGROUND OF THE INVENTION

High sensitivity and amenability to miniaturization for field-portableapplications have helped to make ion mobility spectrometry (IMS) animportant technique for the detection of many compounds, includingnarcotics, explosives, and chemical warfare agents as described, forexample, by G. Eiceman and Z. Karpas in their book entitled “IonMobility Spectrometry” (CRC, Boca Raton, 1994). In IMS, gas-phase ionmobilities are determined using a drift tube with a constant electricfield. Ions are gated into the drift tube and are subsequently separatedin dependence upon differences in their drift velocity. The ion driftvelocity is proportional to the electric field strength at low electricfield strength, for example 200 V/cm, and the mobility, K, which isdetermined from experimentation, is independent of the applied electricfield. Additionally, in IMS the ions travel through a bath gas that isat sufficiently high pressure such that the ions rapidly reach constantvelocity when driven by the force of an electric field that is constantboth in time and location. This is to be clearly distinguished fromthose techniques, most of which are related to mass spectrometry, inwhich the gas pressure is sufficiently low that, if under the influenceof a constant electric field, the ions continue to accelerate.

E. A. Mason and E. W. McDaniel in their book entitled “TransportProperties of Ions in Gases” (Wiley, N.Y., 1988) teach that at highelectric field strength, for instance fields stronger than approximately5,000 V/cm, the ion drift velocity is no longer directly proportional tothe applied field, and K becomes dependent upon the applied electricfield. At high electric field strength, K is better represented byK_(h), a non-constant high field mobility term. The dependence of K_(h)on the applied electric field has been the basis for the development ofhigh field asymmetric waveform ion mobility spectrometry (FAIMS), a termused by the inventors throughout this disclosure, and also referred toas transverse field compensation ion mobility spectrometry, or field ionspectrometry. Ions are separated in FAIMS on the basis of a differencein the mobility of an ion at high field strength, K_(h), relative to themobility of the ion at low field strength, K. In other words, the ionsare separated because of the compound dependent behavior of K_(h) as afunction of the applied electric field strength. FAIMS offers a new toolfor atmospheric pressure gas-phase ion studies since it is the change inion mobility, and not the absolute ion mobility, that is beingmonitored.

The principles of operation of FAIMS using flat plate electrodes havebeen described by I. A. Buryakov, E. V. Krylov, E. G. Nazarov and U. Kh.Rasulev in a paper published in the International Journal of MassSpectrometry and Ion Processes; volume 128 (1993), pp. 143-148, thecontents of which are herein incorporated by reference. The mobility ofa given ion under the influence of an electric field is expressed by:K_(h)=K(1+f(E)), where K_(h) is the mobility of an ion at highelectrical field strength, K is the coefficient of ion mobility at lowelectric field strength and f(E) describes the functional dependence ofthe ion mobility on the electric field strength. Ions are classifiedinto one of three broad categories on the basis of a change in ionmobility as a function of the strength of an applied electric field,specifically: the mobility of type A ions increases with increasingelectric field strength; the mobility of type C ions decreases; and, themobility of type B ions increases initially before decreasing at yethigher field strength. The separation of ions in FAIMS is based uponthese changes in mobility at high electric field strength. Consider anion, for example a type A ion, which is being carried by a gas streambetween two spaced-apart parallel plate electrodes of a FAIMS device.The space between the plates defines an analyzer region in which theseparation of ions occurs. The net motion of the ion between the platesis the sum of a horizontal x-axis component due to the flowing stream ofgas and a transverse y-axis component due to the electric field betweenthe parallel plate electrodes. The term “net motion” refers to theoverall translation that the ion, for instance said type A ion,experiences, even when this translational motion has a more rapidoscillation superimposed upon it. Often, a first plate is maintained atground potential while the second plate has an asymmetric waveform,V(t), applied to it. The asymmetric waveform V(t) is composed of arepeating pattern including a high voltage component, V₁, lasting for ashort period of time t₂ and a lower voltage component, V₂, of oppositepolarity, lasting a longer period of time t₁. The waveform issynthesized such that the integrated voltage-time product, and thus thefield-time product, applied to the plate during each complete cycle ofthe waveform is zero, for instance V₁t₂+V₂t₁=0; for example +2000 V for10 μs followed by −1000 V for 20 μs. The peak voltage during theshorter, high voltage portion of the waveform is called the “dispersionvoltage” or DV in this disclosure.

During the high voltage portion of the waveform, the electric fieldcauses the ion to move with a transverse y-axis velocity componentv₁=K_(h)E_(high), where E_(high) is the applied field, and K_(h) is thehigh field ion mobility under ambient electric field, pressure andtemperature conditions. The distance traveled isd₁=v₁t₂=K_(h)E_(high)t₂, where t₂ is the time period of the applied highvoltage. During the longer duration, opposite polarity, low voltageportion of the asymmetric waveform, the y-axis velocity component of theion is v₂=KE_(low), where K is the low field ion mobility under ambientpressure and temperature conditions. The distance traveled isd₂=v₂t₁=KE_(low)t₁. Since the asymmetric waveform ensures that(V₁t₂)+(V₂t₁)=0, the field-time products E_(high)t₂ and E_(low)t₁ areequal in magnitude. Thus, if K_(h) and K are identical, d₁ and d₂ areequal, and the ion is returned to its original position along the y-axisduring the negative cycle of the waveform, as would be expected if bothportions of the waveform were low voltage. If at E_(high) the mobilityK_(h)>K, the ion experiences a net displacement from its originalposition relative to the y-axis. For example, positive ions of type Atravel farther during the positive portion of the waveform, for instanced₁>d₂, and the type A ion migrates away from the second plate.Similarly, positive ions of type C migrate towards the second plate.

If a positive ion of type A is migrating away from the second plate, aconstant negative dc voltage can be applied to the second plate toreverse, or to “compensate” for, this transverse drift. This dc voltage,called the “compensation voltage” or CV in this disclosure, prevents theion from migrating towards either the second or the first plate. If ionsderived from two compounds respond differently to the applied highstrength electric fields, the ratio of K_(h) to K is similarly differentfor each compound. Consequently, the magnitude of the CV necessary toprevent the drift of the ion toward either plate is also different foreach compound. Thus, when a mixture including several species of ions isbeing analyzed by FAIMS, only one species of ion is selectivelytransmitted for a given combination of CV and DV. The remaining speciesof ions, for instance those ions that are other than selectivelytransmitted through FAIMS, drift towards one of the parallel plateelectrodes of FAIMS and are neutralized. Of course, the speed at whichthe remaining species of ions move towards the electrodes of FAIMSdepends upon the degree to which their high field mobility propertiesdiffer from those of the ions that are selectively transmitted under theprevailing conditions of CV and DV.

An instrument operating according to the FAIMS principle as describedpreviously is an ion filter, capable of selective transmission of onlythose ions with the appropriate ratio of K_(h) to K. In one type ofexperiment using FAIMS devices, the applied CV is scanned with time, forinstance the CV is slowly ramped or optionally the CV is stepped fromone voltage to a next voltage, and a resulting intensity of transmittedions is measured. In this way a CV spectrum showing the total ioncurrent as a function of CV. is obtained. It is a significant limitationof early FAIMS devices which used electrometer detectors, that theidentity of peaks appearing in the CV spectrum are other thanunambiguously confirmed solely on the basis of the CV of transmission ofa species of ion. This limitation is due to the unpredictable,compound-specific dependence of K_(h) on the electric field strength. Inother words, a peak in the CV spectrum is easily assigned to a compounderroneously, since there is no way to predict or even to estimate inadvance, for example from the structure of an ion, where that ion shouldappear in a CV spectrum. In other words, additional information isnecessary in order to improve the likelihood of assigning correctly eachof the peaks in the CV spectrum. For example, subsequent massspectrometric analysis of the selectively transmitted ions greatlyimproves the accuracy of peak assignments of the CV spectrum.

In U.S. Pat. No. 5,420,424 which issued on May 30, 1995, B. L. Carnahanand A. S. Tarassove disclose an improved FAIMS electrode geometry inwhich the flat plates that are used to separate the ions are replacedwith concentric cylinders, the contents of which are herein incorporatedby reference. The concentric cylinder design has several advantages,including higher sensitivity compared to the flat plate configuration,as was discussed by R. W. Purves, R. Guevremont, S. Day, C. W. Pipich,and M. S. Matyjaszczyk in a paper published in Reviews of ScientificInstruments; volume 69 (1998), pp 4094-4105. The higher sensitivity ofthe cylindrical FAIMS is due to a two-dimensional atmospheric pressureion focusing effect that occurs in the analyzer region between theconcentric cylindrical electrodes. When no electrical voltages areapplied to the cylinders, the radial distribution of ions should beapproximately uniform across the FAIMS analyzer. During application ofDV and CV, however, the radial distribution of ions is not uniformacross the annular space of the FAIMS analyzer region. Advantageously,with the application of an appropriate DV and CV for an ion of interest,those ions become focused into a band between the electrodes and therate of loss of ions, as a result of collisions with the FAIMSelectrodes, is reduced. The efficiency of transmission of the ions ofinterest through the analyzer region of FAIMS is thereby improved as aresult of this two-dimensional ion focusing effect.

The focusing of ions by the use of asymmetric waveforms has beendiscussed above. For completeness, the behavior of those ions that arenot focused within the analyzer region of a cylindrical geometry FAIMSis described here, briefly. As discussed previously, those ions havinghigh field ion mobility properties that are other than suitable forfocusing under a given set of DV, CV and geometric conditions will drifttoward one or another wall of the FAIMS device. The rapidity with whichthese ions move towards the wall depends on the degree to which theirK_(h)/K ratio differs from that of the ion that is transmittedselectively under the prevailing conditions. At the very extreme, ionsof completely the wrong property, for instance a type A ion versus atype C ion, are lost to the walls of the FAIMS device very rapidly.

The loss of ions in FAIMS devices should be considered one more way. Ifan ion of type A is focused, for example at DV 2500 volts, CV−11 voltsin a given geometry, it would seem reasonable to expect that the ion isalso focused if the polarity of DV and CV are reversed, for instance DVof −2500 volts and CV of +11 volts. This, however, is not observed andin fact the reversal of polarity in this manner creates a mirror imageeffect of the ion-focusing behavior of FAIMS. The result of suchpolarity reversal is that the ions are not focused, but rather areextremely rapidly rejected from the device,. The mirror image of afocusing valley, is a hill-shaped potential surface. The ions slide tothe center of the bottom of a focusing potential valley (2 or3-dimensions), but slide off of the top of a hill-shaped surface, andhit the wall of an electrode. This is the reason for the existence, inthe cylindrical geometry FAIMS, of the independent “modes” called 1 and2. Such a FAIMS instrument is operated in one of four possible modes:P1, P2, N1, and N2. The “P” and “N” describe the ion polarity, positive(P) and negative (N). The waveform with positive DV, where DV describesthe peak voltage of the high voltage portion of the asymmetric waveform,yields spectra of type P1 and N2, whereas the reversed polarity negativeDV, waveform yields P2 and N1. The discussion thus far has consideredpositive ions but, in general, the same principles apply to negativeions equally.

A further improvement to the cylindrical FAIMS design is realized byproviding a curved surface terminus of the inner electrode. The curvedsurface terminus is continuous with the cylindrical shape of the innerelectrode and is aligned co-axially with an ion-outlet orifice of theFAIMS analyzer region. The application of an asymmetric waveform to theinner electrode results in the normal ion-focusing behavior describedabove, except that the ion-focusing action extends around the generallyspherically shaped terminus of the inner electrode. This means that theselectively transmitted ions cannot escape from the region around theterminus of the inner electrode. This only occurs if the voltagesapplied to the inner electrode are the appropriate combination of CV andDV as described in the discussion above relating to 2-dimensionalfocusing. If the CV and DV are suitable for the focusing of an ion inthe FAIMS analyzer region, and the physical geometry of the innersurface of the outer electrode does not disturb this balance, the ionswill collect within a three-dimensional region of space near theterminus. Several contradictory forces are acting on the ions in thisregion near the terminus of the inner electrode. The force of thecarrier gas flow tends to influence the ion cloud to travel towards theion-outlet orifice, which advantageously also prevents the trapped ionsfrom migrating in a reverse direction, back towards the ionizationsource. Additionally, the ions that get too close to the inner electrodeare pushed back away from the inner electrode, and those near the outerelectrode migrate back towards the inner electrode, due to the focusingaction of the applied electric fields. When all forces acting upon theions are balanced, the ions are effectively captured in every direction,either by forces of the flowing gas, or by the focusing effect of theelectric fields of the FAIMS mechanism. This is an example of athree-dimensional atmospheric pressure ion trap, as disclosed in acopending PCT application in the name of R. Guevremont and R. Purves,the contents of which are herein incorporated by reference.

Ion focusing and ion trapping requires electric fields that are otherthan constant in space, normally occurring in a geometricalconfiguration of FAIMS in which the electrodes are curved, and/or arenot parallel to each other. For example, a non-constant in spaceelectric field is created using electrodes that are cylinders or a pratthereof; electrodes that are spheres or a part thereof: electrodes thatare elliptical spheres or a part thereof; and, electrodes that areconical or a part thereof. Optionally, various combinations of theseelectrode shapes are used.

As discussed above, one previous limitation of the cylindrical FAIMStechnology is that the identity of the peaks appearing in the CV spectraare not unambiguously confirmed due to the unpredictable changes inK_(h) at high electric field strengths. Thus, one way to extend thecapability of instruments based on the FAIMS concept is to provide a wayto determine the make-up of the CV spectra more accurately, such as byintroducing ions from the FAIMS device into a mass spectrometer formass-to-charge (m/z) analysis. Advantageously, the ion focusing propertyof cylindrical FAIMS devices acts to enhance the efficiency fortransporting ions from the analyzer region of a FAIMS device into anexternal sampling orifice, for instance an inlet of a mass spectrometer.This improved efficiency of transporting ions into the inlet of the massspectrometer is optionally maximized by using a 3-dimensional trappingversion of FAIMS operated in nearly trapping conditions. Undernear-trapping conditions, the ions that have accumulated in thethree-dimensional region of space near the spherical terminus of theinner electrode are caused to leak from this region, being pulled by aflow of gas towards the ion-outlet orifice. The ions that leak out fromthis region do so as a narrow, approximately-collimated beam, which ispulled by the gas flow through the ion-outlet orifice and into a smallorifice leading into the vacuum system of a mass spectrometer.

Additionally, the resolution of a FAIMS device is defined in terms ofthe extent to which ions having similar mobility properties as afunction of electric field strength are separated under a set ofpredetermined operating conditions. Thus, a high-resolution FAIMS devicetransmits selectively a relatively small range of different ion specieshaving similar mobility properties, whereas a low-resolution FAIMSdevice transmits selectively a relatively large range of different ionspecies having similar mobility properties. The resolution of FAIMS in acylindrical geometry FAIMS is compromised relative to the resolution ina parallel plate geometry FAIMS because the cylindrical geometry FAIMShas the capability of focusing ions. This focusing action means thations of a wider range of mobility characteristics are simultaneouslyfocused in the analyzer region of the cylindrical geometry FAIMS. Acylindrical geometry FAIMS with narrow electrodes has the strongestfocusing action, but the lowest resolution for separation of ions. Asthe radii of curvature are increased, the focusing action becomesweaker, and the ability of FAIMS to simultaneously focus ions of similarhigh-field mobility characteristics is similarly decreased. This meansthat the resolution of FAIMS increases as the radii of the electrodesare increased, with parallel plate geometry FAIMS having the maximumattainable resolution.

Note that, while the above discussion refers to the ions as being“captured” or “trapped”, in fact, the ions are subject to continuous‘diffusion’. Diffusion always acts contrary to focusing and trapping.The ions always require an electrical, or gas flow force to reverse theprocess of diffusion. Thus, although the ions are focused into animaginary cylindrical zone in space with almost zero thickness, orwithin a 3-dimensional ion trap, in reality it is well known that theions are actually dispersed in the vicinity of this idealized zone inspace because of diffusion. This is important, and should be recognizedas a global feature superimposed upon all of the ion motions discussedin this disclosure. This means that, for example, a 3-dimensional iontrap actually has real spatial width, and ions continuously leak fromthe 3-dimensional ion trap, for several physical, and chemical reasons.Of course, the ions occupy a smaller physical region of space if thetrapping potential well is deeper.

The analysis of certain samples, for instance inorganic compoundscontaining metal atoms, requires an ionization source based upon aplasma torch to produce the ions for analysis. Unfortunately, a priorart inductively couple plasma (ICP) source also produces an abundance ofions resulting from ionization of the bath gas molecules or atoms. Theplasma is not a selective ionization source, and significant backgroundion intensity relative to the trace ions of interest is typicallyproduced. Further unfortunately, the plasma in some cases producesinterfering ions having a same mass-to-charge ratio (m/z) as the ions ofinterest. For example, ions of the structure argon oxide (ArO+) with m/z56 are produced in an argon plasma, and are isobaric with the analyteion of iron (Fe+) also with m/z 56.

It would be advantageous to provide a method and a system for reducingthe intensity of the background ions produced within a plasma sourcethat are transmitted to a mass analyzer with the ions of interest. Itwould be further advantageous to provide a method and a system toseparate ions of interest from interfering ions having a same m/z ratiothat are formed in the plasma source.

OBJECT OF THE INVENTION

In order to overcome these and other limitations of the prior art, it isan object of the present invention to provide an apparatus forseparating ions produced by an ICP and having a substantially samemass-to-charge ratio prior to providing the ions to a mass analyzer fordetection.

SUMMARY OF THE INVENTION

In accordance with the invention there is provided an analyzercomprising: an inductively coupled plasma/mass spectrometer comprising aplasma ionization source for producing ions and a mass analyzer within alow pressure region, characterized in that between the plasma ionizationsource and the mass analyzer is disposed a FAIMS analyzer.

In accordance with the invention there is provided a method forseparating ions comprising the steps of:

producing ions within an inductively coupled plasma ionization source;

providing an asymmetric waveform to an electrode for forming an electricfield within the FAIMS analyzer region to support selective transmissionof ions within the FAIMS analyzer region;

transporting the ions through the electric field to perform a separationthereof; and,

providing the ions after separation to a mass spectrometer for analysis.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows three possible examples of changes in ion mobility as afunction of the strength of an electric field;

FIG. 2a illustrates the trajectory of an ion between two parallel plateelectrodes under the influence of the electrical potential V(t);

FIG. 2b shows an asymmetric waveform described by V(t);

FIG. 3 shows a simplified block diagram of an ICP/FAIMS/MS systemaccording to a first embodiment of the invention;

FIG. 4 shows a simplified block diagram of an ICP/FAIMS/MS systemaccording to a second embodiment of the invention;

FIG. 5 shows a simplified block diagram of an ICP/FAIMS/MS systemaccording to a third embodiment of the invention; and,

FIG. 5a shows a cross sectional view taken along the line A-B in FIG. 5.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIG. 1, shown are three possible examples of the change inion mobility properties with increasing electric field strength, as wasdiscussed previously. The separation of ions in FAIMS is based upon adifference in these mobility properties for a first ion relative to asecond ion. For instance, a first type A ion having a low field mobilityK_(1,low) is other than separated in a FAIMS device from a second type Aion having a second different low field mobility K_(2,low), if under theinfluence of high electric field strength, the ratioK_(1,high)/K_(1,low) is equal to the ratio K_(2,high)/K_(2,low).Interestingly, however, this same separation is achieved usingconventional ion mobility spectrometry, which is based on a differencein ion mobilities at low applied electric field strength.

Referring to FIG. 2a, shown is a schematic diagram illustrating themechanism of ion separation according to the FAIMS principle. An ion 1,for instance a positively charged type A ion, is carried by a gas stream2 flowing between two spaced apart parallel plate electrodes 3 and 4.One of the plates 4 is maintained at ground potential while the otherplate 3 has an asymmetric waveform described by V(t), applied to it. Thepeak voltage applied during the waveform is called the dispersionvoltage (DV), as is shown in FIG. 2b. Referring still to FIG. 2b, thewaveform is synthesized so that the electric fields during the twoperiods of time t_(high) and t_(low) are not equal. If K_(h) and K areidentical at high and low fields, the ion 1 is returned to its originalposition at the end of one cycle of the waveform. However, underconditions of sufficiently high electric fields, K_(h) is greater than Kand the distances traveled during t_(high) and t_(low) are no longeridentical. Within an analyzer region defined by a space 8 between thefirst and second spaced apart electrode plates, 3 and 4, respectively,the ion 1 experiences a net displacement from its original positionrelative to the plates 3 and 4 as illustrated by the dashed line 5 inFIG. 2a.

If a type A ion is migrating away from the upper plate 3, a constantnegative dc compensation voltage CV is applied to plate 3 to reverse or“compensate” for this offset drift. Thus, the ion 1 does not traveltoward either plate. If two species of ions respond differently to theapplied high electric field, for instance the ratios of K_(h) to K arenot identical, the compensation voltages necessary to prevent theirdrift toward either plate are similarly different. To analyze a mixtureof ions, the compensation voltage is, for example, scanned to transmiteach of the components of a mixture in turn. This produces acompensation voltage spectrum, or CV spectrum.

Referring to FIG. 3, a simplified block diagram of an ICP/FAIMS/MSsystem according to a first embodiment of the invention is shown. Twoelectrodes 9 and 10, defining a FAIMS analyzer region 16 therebetween,are disposed on the low pressure side of an orifice plate 11, forexample within a differentially pumped region of an interface leadinginto a mass analyzer shown generally at 12. The ions are produced by aninductively couple plasma 13 which is supported in a special torchassembly 23 in a known manner. For the sake of clarity and brevity, thegas flow system, and the electrical and electronic components, forexample power supplies, that are necessary to establish the plasma arenot shown in FIG. 3.

Still referring to FIG. 3, an asymmetric waveform and a low voltage dccompensation voltage is applied to electrode 9 by a power supply 14. Inthis embodiment FAIMS is operating at a gas pressure lower than standardatmospheric pressure, such that the voltage necessary to effect a changein ion mobility characteristic of high electric field is reducedcompared to the voltage required at approximately atmospheric pressure.For instance, the effect of electric field strength on ion mobility isconsidered in terms of E/N, where E is the electric field strength and Nis the number density of the bath gas. For example, if a DV of 3000volts is necessary to achieve a desired effect at atmospheric pressure,the same effect is obtained at DV of 300 volts when the gas pressure isreduced to 0.1 of an atmosphere. This relationship between fieldstrength and gas number density well known for FAIMS apparatus withelectrode geometries based upon one of two parallel plates and twoconcentric substantially overlapping cylinders. At higher E/N thefrequency of the waveform may be increased in order to limit thedistances of the ion trajectory during each cycle of the waveform, thusminimizing ion loss through collisions with the electrodes.

Still referring to FIG. 3, the applied DV is lower than the DV that isneeded to operate FAIMS at substantially atmospheric pressure. The twoFAIMS electrodes 9 and 10 are curved electrodes in spaced apart stackedarrangement, such that an approximately uniform spacing is maintainedbetween the electrodes 9 and 10 along the FAIMS analyzer region 16.Advantageously, the curvature along the electrode bodies 9 and 10results in the formation of electric fields within analyzer region 16that are non-uniform in space by the application of the voltages bypower supply 14. This non-uniform in space electric field is optionallyproduced by making the FAIMS electrodes substantially cylindrical orspherical in shape, however, many other shapes and combinations ofshapes are used to achieve the same effect.

The ions that pass through an orifice 15 in the orifice plate 11 arecarried to the FAIMS analyzer region 16 between electrodes 9 and 10 by aflow of a carrier gas originating from the gas passing into the lowpressure region through the orifice 15. Those ions having theappropriate high field-strength mobility properties for transmissionunder the conditions of DV and CV are focused in the analyzer region 16and selectively transmitted to a skimmer cone 17. The ions aretransported through the analyzer region 16 by the carrier gas whichflows toward a gap 18 between the FAIMS analyzer region 16 and theskimmer cone 17. The skimmer cone 17 is within a chamber 19 of aninterface leading into the mass spectrometer 12, the chamber 19 isevacuated to low gas pressure in the vicinity of the gap 18 by amechanical pump (not shown) connected to the chamber 19. A gas barrier20 serves to ensure that the gas pressure in the vicinity of the gap 18is slightly lower than the pressure near the region 21 immediatelybehind orifice 15. Since the pressure in region 21 is higher than thepressure in the gap 18, the carrier gas flows along the FAIMS analyzerregion in a direction generally towards the gap 18. Of course, othermeans for transporting the ions through the FAIMS analyzer region 16 areoptionally provided, for instance an electric field.

Still referring to FIG. 3, the ions that are selectively transmittedthrough the FAIMS analyzer region 16 are transferred to the massspectrometer through the orifice 22 in skimmer cone 17. The ions aredirected toward the orifice 22 of skimmer cone 17 by an electric fieldformed between FAIMS and the skimmer cone 17, the electric fieldproduced by the application of dc voltages to the FAIMS and to theskimmer cone 17.

Of course, the hot argon plasma of a conventional ICP is not compatiblewith FAIMS, and the FAIMS is located within the first lowpressure-chamber of the mass spectrometer as previously described withreference to the first embodiment of the present invention shown in FIG.3. Optionally, additional provisions for thermally isolating the FAIMSanalyzer from the ICP source are provided. Further optionally, a coolingsystem is provided to maintain the vicinity of the FAIMS analyzer atapproximately ambient laboratory temperature.

Referring to FIG. 4, a simplified block diagram of an ICP/FAIMS/MSsystem according to a second embodiment of the invention is shown. TwoFAIMS electrodes 41 and 42 defining a FAIMS analyzer region 43therebetween, are disposed on the low pressure side of an orifice plate11, for example within a differentially pumped region of an interfaceleading into a mass analyzer shown generally at 12. The ions areproduced by an inductively couple plasma 13 which is supported in aspecial torch assembly 23 in a known manner. For the sake of clarity andbrevity, the gas flow system, and the electrical and electroniccomponents, for example power supplies, that are necessary to establishthe plasma are not shown in FIG. 3.

Still referring to FIG. 4, an asymmetric waveform and a low voltage dccompensation voltage is applied to electrode 42 by a power supply 14. Inthis embodiment FAIMS is operating at a gas pressure lower than standardatmospheric pressure, such that the voltage necessary to effect a changein ion mobility characteristic of high electric field is reducedcompared to the voltage required at approximately atmospheric pressure.For instance, the effect of electric field strength on ion mobility isconsidered in terms of E/N, where E is the electric field strength and Nis the number density of the bath gas. For example, if a DV of 3000volts is necessary to achieve a desired effect at atmospheric pressure,the same effect is obtained at DV of 300 volts when the gas pressure isreduced to 0.1 of an atmosphere. This relationship between fieldstrength and gas number density well known for FAIMS apparatus withelectrode geometries based upon one of two parallel plates and twoconcentric substantially overlapping cylinders. At higher E/N thefrequency of the waveform may be increased in order to limit thedistances of the ion trajectory during each cycle of the waveform, thusminimizing ion loss through collisions with the electrodes.

Referring still to FIG. 4, the electrodes 41 and 42 are provided ascurved plates in a spaced apart stacked arrangement such that such thatan approximately uniform spacing is maintained between the electrodes 41and 42 along the FAIMS analyzer region 43. Advantageously, the curvatureacross the electrode bodies 41 and 42 results in the formation ofelectric fields within analyzer region 43 that are non-uniform in spaceby the application of the voltages by power supply 14. This non-uniformin space electric field is optionally produced by making the FAIMSelectrodes substantially cylindrical or spherical in shape, however,many other shapes and combinations of shapes are used to achieve thesame effect. The curvature of the plates is shown most clearly in aninset view at the top of FIG. 4. In this inset view, the ions travelinto and out of the plane of the drawing.

Still referring to FIG. 4, the ions that pass through an orifice 15 inthe orifice plate 11 are carried to the FAIMS analyzer region 43 betweenelectrodes 41 and 42 by a flow of a carrier gas originating from the gaspassing into the low pressure region through the orifice 15. Those ionshaving the appropriate high field-strength mobility properties fortransmission under the conditions of DV and CV are focused in theanalyzer region 16 and selectively transmitted to a skimmer cone 17. Theions are transported through the analyzer region 43 by the carrier gas,which flows toward a gap 18 between the FAIMS analyzer region 43 and theskimmer cone 17. The skimmer cone 17 is within a chamber 19 of aninterface leading into the mass spectrometer 12, the chamber 19 isevacuated to low gas pressure in the vicinity of the gap 18 by amechanical pump (not shown) connected to the chamber 19. A gas barrier44 serves to ensure that the gas pressure in the vicinity of the gap 18is slightly lower than the pressure near the region 21 immediatelybehind orifice 15. Since the pressure in region 21 is higher than thepressure in the gap 18, the carrier gas flows along the FAIMS analyzerregion in a direction generally towards the gap 18. Of course, othermeans for transporting the ions through the FAIMS analyzer region 43 areoptionally provided, for instance an electric field.

Still referring to FIG. 4, the ions that are selectively transmittedthrough the FAIMS analyzer region 43 are transferred to the massspectrometer 12 through the orifice 22 in skimmer cone 17. The ions aredirected toward the orifice 22 of skimmer cone 17 by an electric fieldformed between FAIMS and the skimmer cone 17, the electric fieldproduced by the application of dc voltages to the FAIMS and to theskimmer cone 17.

Of course, FAIMS electrodes 41 and 42 are optionally provided with ashape other than curved plates, for instance as flat parallel plateelectrodes. However, in order to efficiently extract the selectivelytransmitted ions from a FAIMS analyzer region defined by the spacebetween flat plate electrodes, a third approximately equally spaced flatplate electrode is additionally required, as disclosed in a co-pendingPCT application in the name of R. Guevremont and R. Purves, the contentsof which are herein incorporated by reference.

Of course, the hot argon gas (plasma) of a conventional ICP is notcompatible with FAIMS, and the FAIMS is located within the first lowpressure-chamber of the mass spectrometer as previously described withreference to the second embodiment of the present invention shown inFIG. 4. Optionally, additional provisions for thermally isolating theFAIMS analyzer from the ICP source are provided. Further optionally, acooling system is provided to maintain the vicinity of the FAIMSanalyzer at approximately ambient laboratory temperature.

Referring to FIG. 5, a simplified block diagram of an ICP/FAIMS/MSsystem according to a third embodiment of the invention is shown. ThreeFAIMS electrodes 51 and 52 defining a FAIMS analyzer region 54therebetween, are disposed on th low pressure side of an orifice plate11, for example within a differentially pumped region fan interfaceleading into a mass analyzer shown generally at 12. The ions areproduced b an inductively couple plasma 13 which is supported in aspecial torch assembly 3 in a known manner. For the sake of clarity andbrevity, the gas flow system, and the electrical and electroniccomponents, for example power supplies, that are necessary to establishthe plasma are not shown in FIG. 5.

Still referring to FIG. 5, an asymmetric waveform and a low voltage dccompensation voltage is applied to FAIMS middle electrode 52 by a powersupply 14. In this embodiment FAIMS is operating at a gas pressure lowerthan standard atmospheric pressure, such that the voltage necessary toeffect a change in ion mobility characteristic of high electric field isreduced compared to the voltage required at approximately atmosphericpressure. For instance, the effect of electric field strength on ionmobility is considered in terms of E/N, where E is the electric fieldstrength and N is the number density of the bath gas. For example, if aDV of 3000 volts is necessary to achieve a desired effect at atmosphericpressure, the same effect is obtained at DV of 300 volts when the gaspressure is reduced to 0.1 of an atmosphere. This relationship betweenfield strength and gas number density well known for FAIMS apparatuswith electrode geometries based upon one of two parallel plates and twoconcentric substantially overlapping cylinders. At higher E/N thefrequency of the waveform may be increased in order to limit thedistances of the ion trajectory during each cycle of the waveform, thusminimizing ion loss through collisions with the electrodes.

Referring still to FIG. 5, the electrodes 51, 52 and 53 are providedcurved plates in a spaced apart stacked arrangement such that such thatan approximately uniform spacing is maintained between the electrodes 51and 52 along the FAIMS analyzer region 54, and a substantially sameuniform spacing is maintained between the electrodes 52 and 53 along theFAIMS analyzer region 55. Advantageously, the curvature across theelectrode bodies 51, 52 and 53 results in the formation of electricfields within analyzer region 54 and 55 that are non-uniform in space,by the application of the voltages by power supply 14. This non-uniformin space electric field is optionally produced by making the FAIMSelectrodes substantially cylindrical or spherical in shape, however,many other shapes and combinations of shapes are used to achieve thesame effect. The curvature of the plates is shown most clearly at FIG.5a. which is a cross sectional view taken alone the line A-B In FIG. 5a,the ions travel into and out of the plane of the drawing.

Of course, the non-constant in space electric field established withinanalyzer region 54 between the FAIMS electrodes 51 and 52 is a differentnon-constant in space electric field compared to the electric field thatis established within analyzer region 55 between the FAIMS electrodes 51and 52. A first species of ions having first mobility properties as afunction of electric field strength are selectively transmitted withinanalyzer region 54, and a second different species of ions having seconddifferent mobility properties a function of electric field strength areselectively transmitted within analyzer region 55 in parallel with thefirst species of ion.

Still referring to FIG. 5, the ions that pass through an orifice 15 inthe orifice plate 11 are carried to one of the FAIMS analyzer regions 54and 55 between electrodes 51 and 52, and between electrodes 52 and 53,respectively, by a flow of a carrier gas originating from the gaspassing into the low pressure region through the orifice 15. Those ionshaving the appropriate high field-strength mobility properties fortransmission under the conditions of DV and CV are focused within one ofthe FAIMS analyzer regions, for instance FAIMS analyzer region 54, andselectively transmitted to a skimmer cone 17. Of course, other speciesof ions will be focused within the FAIMS analyzer region 55. The ionsare transported through the analyzer region 54 by the carrier gas whichflows toward a gap 18 between the FAIMS analyzer region 54 and theskimmer cone 17. The skimmer cone 17 is within a chamber 19 of aninterface leading into the mass spectrometer 12, the chamber 19 isevacuated to low gas pressure in the vicinity of the gap 18 by amechanical pump (not shown) connected to the chamber 19. A gas barrier44 serves to ensure that the gas pressure in the vicinity of the gap 18is slightly lower than the pressure near the region 21 immediatelybehind orifice 15. Since the pressure in region 21 is higher than thepressure in the gap 18, the carrier gas flows along the FAIMS analyzerregion in a direction generally towards the gap 18. Optionally, theleading and trailing edges of at least curved electrode plate 52 areprovided with curved edges for focusing the ions and for diverting theions away from the electrode 52 such that the ions other than collidetherewith, thereby improving ion transmission efficiency. Of course,other means for transporting the ions through the FAIMS analyzer regions54 and 55 are optionally provided, for instance an electric field.

Still referring to FIG. 5, the ions that are selectively transmittedthrough the FAIMS analyzer region 54 are transferred to the massspectrometer 12 through the orifice 22 in skimmer cone 17. The ions aredirected toward the orifice 22 of skimmer cone 17 by an electric fieldformed between FAIMS and the skimmer cone 17, the electric fieldproduced by the application of de voltages to the FAIMS and to theskimmer cone 17.

Of course, the hot argon plasma of a conventional ICP is not compatiblewith FAIMS, and the FAIMS is located within the first lowpressure-chamber of the mass spectrometer as previously described withreference to the third embodiment of the present invention shown in FIG.5. Optionally, additional provisions for thermally isolating the FAIMSanalyzer from the ICP source are provided. Further optionally, a coolingsystem is provided to maintain the vicinity of the FAIMS analyzer atapproximately ambient laboratory temperature.

It will be obvious to one of skill in the art that separating differentionic species having identical mass-to-charge ratios is other thanpossible using a prior art mass spectrometer absent FAIMS. Further, itwill be obvious to one of skill in the art that separating differentionic species having similar mass-to-charge ratios, for instancemass-to-charge ratios that differ only by several hundredths of anatomic mass unit (amu), requires a high resolution mass spectrometer. Itis a disadvantage of high resolution mass spectrometers that the initialcapital cost of purchase is high, and it is a further disadvantage thatthe ongoing operating costs of providing an expert operator andexpensive pumping apparatus are also high. Additionally, a highresolution mass spectrometer suffers from lower sensitivity compared tolow resolution mass spectrometers, such that a system including a highresolution mass spectrometer as part of a detection systems suffers froman overall lower ion transmission efficiency and a resultant decreasedsensitivity.

It is an advantage of the present invention as described with referenceto the first, second and third embodiments that FAIMS optionallyseparates ions produced by the ICP source which have equal m/z. FAIMSseparates ions in dependence upon a difference in ion mobilityproperties as a function of electric field strength, and thereforeeffects the separation of ionic species that are other than separated inthe mass spectrometer 12. For instance an appropriate combination of DVand CV is applied to at least an electrode of FAIMS to selectivelytransmit an analyte ion through the FAIMS analyzer region to passthrough an orifice leading to a low resolution mass spectrometer. Thoseions that are other than of interest and which have mobility propertiesthat are other than suitable for being selectively transmitted throughthe FAIMS analyzer region, for instance the background ions, are causedto collide with a part of FAIMS and are rejected from the device. Sincethe number of analyte ions arriving at the mass spectrometer relative tothe number of background ions is increased, the detector responserelative to the level of the noise is also increased, such that thesensitivity of the instrument is increased. Optionally, the geometry ofthe FAIMS electrodes is selected to maximize ion transmission efficiencythrough FAIMS, such that the sensitivity of an ICP/FAIMS/MS instrumentis improved further.

It is a further advantage of FAIMS that the capability of FAIMS toseparate ions having similar high field mobility properties improves asthe m/z ratio of the ion is decreased. This is consistent with therequirements of the system described herein, where FAIMS is required toseparate ions of typically low m/z values, for instance argon oxide(ArO+) with m/z 56 and the ion of iron (Fe+) also with m/z 56. Thetypically low mass-to-charge values of the ions of interest is alsoconsistent with the operation of a very inexpensive, low resolution massspectrometer. Advantageously, in addition to improving sensitivity forthe detection of analyte ions and removing isobaric ions interferingwith the analysis the analyte ions, the ICP/FAIMS/MS system of thepresent invention is compact, inexpensive and simpler to operatecompared to a prior art ICP/high-resolution mass spectrometer.

Further advantageously, FAIMS separates the ions of interest from theabundance of background ions that are other than of interest formed inthe plasma.

Of course, numerous other embodiments could be envisioned, withoutdeparting significantly from the teachings of the present invention.

What is claimed is:
 1. An analyzer comprising: an inductively coupledplasma/mass spectrometer comprising a plasma ionization source forproducing ions and a mass analyzer within a low pressure region,characterized in that between the plasma ionization source and the massanalyzer is disposed a FAIMS analyzer, the FAIMS analyzer comprising twospaced apart electrodes defining a FAIMS analyzer reunion therebetweenand having a first ion inlet for introducing ions into the FAIMSanalyzer region and a first ion outlet for extracting ions from theFAIMS analyzer region; and, an orifice plate having a second ion outletfor providing ions from the plasma ionization source to the first ioninlet, wherein the FAIMS analyzer is disposed on a low pressure side ofthe orifice plate.
 2. An apparatus according to claim 1 wherein the twospaced apart electrodes are curved electrodes.
 3. An apparatus accordingto claim 1 wherein the FAIMS analyzer comprises a gas inlet forproviding a flow of at least a gas through the analyzer region betweenthe two spaced apart electrodes for transporting the ions through theanalyzer region in a direction generally towards the first ion outlet.4. An apparatus according to claim 1 wherein the FAIMS comprises a firstgas inlet for providing a flow of at least a gas through the analyzerregion for, in use, directing at least some of the ions generallytowards the first ion outlet.
 5. An apparatus according to claim 1comprising an electrode for providing an electric field for selectivelytransporting the ions generally towards the first ion outlet.
 6. Anapparatus according to claim 1 comprising a voltage source for providinga signal to the electrode for providing an electric field forselectively transporting the ions generally towards the first ionoutlet.
 7. A method for separating ions comprising the steps of:producing ions within an inductively coupled plasma ionization source;providing an electrode of a FAIMS analyzer within a low pressure region;providing an asymmetric waveform and a direct current compensationvoltage to the electrode for forming an electric field within the FAIMSanalyzer region to support selective transmission of ions within theFAIMS analyzer region; transporting the produced ions through theelectric field to perform a separation thereof; and, providing the ionsafter separation to a mass spectrometer for analysis.
 8. A methodaccording to claim 7 wherein the step of transporting includes the stepof providing a flow of at least a gas through the analyzer region.
 9. Amethod according to claim 7 wherein the step of transporting includesthe step of providing an electric field for selectively transporting theions in a direction generally towards the mass spectrometer.